Autophagy gene-dependent clearance of apoptotic cells during embryonic development.

By X. Qu, Z. Zou, Qihua Sun, K. Luby‐Phelps, P. Cheng, R. Hogan, Christopher Gilpin, Beth Levine. Cell, 2007

673 citations recorded by the source corpus.

Autophagy is commonly observed in metazoan organisms during programmed cell death (PCD), but its function in dying cells has been unclear. We studied the role of autophagy in embryonic cavitation, the earliest PCD process in mammalian development. Embryoid bodies (EBs) derived from cells lacking the autophagy genes, atg5 or beclin 1, fail to cavitate. This defect is due to persistence of cell corpses, rather than impairment of PCD. Dying cells in autophagy gene null EBs fail to express the "eat-me" signal, phosphatidylserine exposure, and secrete lower levels of the "come-get-me" signal, lysophosphatidylcholine. These defects are associated with low levels of cellular ATP and are reversed by treatment with the metabolic substrate, methylpyruvate. Moreover, mice lacking atg5 display a defect in apoptotic corpse engulfment during embryonic development. We conclude that autophagy contributes to dead-cell clearance during PCD by a mechanism that likely involves the generation of energy-dependent engulfment signals.

Subfields: Epidemiology, Immunology, Water Science and Technology

View Paper: https://www.semanticscholar.org/paper/9b7a30f154bbd69cbc71c18754721b8d923463c6

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Epidemiology

1. Beth Levine
2. Guido Kroemer
3. N. Mizushima
4. Douglas R. Green
5. I. Slaninová
6. D. Tang
7. R. Kang
8. D. Klionsky

In Immunology

1. Guido Kroemer
2. Beth Levine
3. L. Zitvogel
4. Douglas R. Green
5. N. Mizushima
6. H. J. Zeh
7. D. Tang
8. R. Kang

Citations in the corpus

• Ferroptosis in infection, inflammation, and immunity (2021, background): “Clearing these dead cell corpses without destroying healthy neighboring cells through phagocytosis (within tissues) or shedding (from epithelial surfaces) plays a vital role in sustaining cell homeostasis (Boada-Romero et al., 2020; Doran et al., 2020; Martinez et al., 2011; Qu et al., 2007).”
• Macrophage Autophagy Plays a Protective Role in Advanced Atherosclerosis (2012, background): “In an attempt to increase our understanding in these areas, we decided to explore the process of autophagy, which can affect both apoptosis and efferocytosis in other settings (EisenbergLerner et al., 2009; Qu et al., 2007).”
• Autophagic cell death: the story of a misnomer (2008, background): “For example, one marker of apoptotic cell death is phosphatidylserine exposure on the plasma membrane and, at least in a mouse embryonic developmental model system, this process requires ATG -dependent ATP production in dying cell”
• Autophagy as a target for anticancer therapy (2011, background): “Beclin1 −/− mutant mice died early in embryonic development”
• Autophagy in immunity and inflammation (2011, background): “Autophagy genes are essential for the heterophagic clearance of dying apoptotic cells during developmental programmed cell death (by the generation of ATP-dependent engulfment signals) 84 , and the retinas and lungs of embryonic mice lacking Atg5 have a defect in apoptotic corpse engulfment that is ”
• Neuronal Cell Death. (2018, positive): “, in phagocytes to enable phagocytosis of dead cells in the developing retina and to enable cavitation of embryoid bodies (461, 554).”
• To be or not to be? How selective autophagy and cell death govern cell fate. (2014, neutral): “Intriguingly, the autophagic process has been implicated in PS exposure on some but perhaps not all cells (Qu et al., 2007; Mellé n et al., 2008).”
• Autophagy in mammalian development and differentiation (2010, background): “Fourth, the clearance of apoptotic corpses is defective in Atg5 −/− late embryos, which might also contribute to developmental abnormalitie”
• Autophagy: assays and artifacts (2010, background): “Tissue-specific knockout of Atg5 or Atg7 in brain led to the early onset of neurodegeneration and progressive deficits in motor function [49,50], while loss of Beclin 1 (Atg6) resulted in early embryonic lethality characterized by widespread cell death, abnormal ectodermal layer with reduced cavitat”
• Growth arrest and autophagy are required for salivary gland cell degradation in Drosophila. (2007, positive): “A recent study showed that autophagy is required to generate the energy needed to promote phagocytosis signaling in an in vitro model of embryonic cavitation (Qu et al., 2007).”